The classification of cessation of renal function into acute and chronic renal failure demarcates disease states that are distinct in etiology, pathogenesis, rate of loss of renal function, potential for recovery of renal function and therapeutic strategies applied in their management. Chronic renal failure is characterized by an inexorable loss of renal function, which can last for several years after the initial presentation of renal insufficiency, culminating in end-stage disease. The arrival of end-stage disease signifies irretrievable loss of renal function and necessitates replacement of renal function by dialysis or transplantation. The leading causes of chronic renal failure are assorted glomerulonephritides, diabetic nephropathy, chronic tubulointerstitial diseases and polycystic kidney diseases. See F. N. Ziyadeh, Textbook of Internal Medicine, Vol. 1, W. E. Kelley, ed., J. B. Lippincott Co., Philadelphia (1989) at pages 883-889; M. Walser, Kid. Int., 37, 1195 (1990).
Management of patients with chronic renal failure utilizes strategies that retard the rate of loss of renal function, thereby delaying the onset of end-stage disease. Such therapeutic strategies include treatment of systemic hypertension, correction of perturbed calcium/phosphate homeostasis and restriction in dietary protein intake (W. E. Mitch, Ann. Rev. Med., 35, 249 (1984)). Some studies have indicated that dietary supplementation with alpha-keto acids in conjunction with restricted protein and phosphate intake may be efficacious in retarding the progression of established renal disease (W. E. Mitch et al., N. Engl. J. Med., 311, 623 (1984)). The mechanism by which dietary supplementation with alpha-keto acids may act to alleviate progressive renal injury is unknown.
Acute renal failure is characterized by a relatively abrupt decline in renal function. Temporary replacement of renal function by dialysis may be indicated within days of the instigating insult and may be necessary for several weeks during the maintenance phase of acute renal failure. While recovery of renal function usually occurs, there is substantial morbidity and mortality during the initiation, maintenance and recovery phases of acute renal failure. The recovery phase of acute renal failure, once complete, usually allows the resumption of normal renal function. Conditions that predispose to acute renal failure include ineffective renal perfusion, systemic hypotension of any cause, sepsis, major trauma, nephrotoxic insults such as aminoglycoside antibiotics and radiographic contrast agents, and obstruction to the urinary tract (M. Brezis et al., The Kidney, B. M. Brenner et al., eds., W. B. Saunders (3rd ed. 1986) at pages 735-799). Less commonly, acute renal failure may arise from certain types of glomerulonephritis and vasculitis.
Since there are no specific therapeutic maneuvers that consistently and effectively hasten the recovery of renal function, once acute renal failure has already occurred, the management of patients with acute renal failure emphasizes the avoidance and/or correction of conditions such as hypoperfusion, hypotension, sepsis and nephrotoxic agents that predispose to acute renal failure (C. M. Kjellstrand et al., Diseases of the Kidney, R. W. Schrier et al., eds., Little Brown Co., Boston (4th ed. 1988) at pages 1501-1542).
Therefore, there is a continuing need for effective therapies to arrest or prevent acute renal failure in susceptible patients.